Sodium activated potassium channels (K(Na)) are modulated by nicotinamide adenine dinucleotide (NAD+) in adult dorsal root ganglion (DRG) neurons
Tamsett, Thomas J.
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Dorsal root ganglia consist of small, nociceptive neurons and large proprioceptive neurons that transduce external sensory stimuli to the central nervous system through the firing of action potentials. Potassium channels can shape action potentials, set resting membrane potential and determine firing frequency of neurons. A novel type of potassium channel, the sodium activated potassium channel (K Na ), found abundantly expressed in DRG neurons has been suggested to control neuronal excitability; however, this is not clearly understood because normally large Na + concentrations are required to activate these channels. In this study, we examined the modulation of K Na channels, by the metabolic coenzyme nicotinamide adenine dinucleotide (NAD + ). Using inside-out excised patch recordings of large and small DRG neurons and establishing K Na channel Na + dose-response relationships, we demonstrated a decrease in Na + EC 50 from ∼50mM to ∼20mM when NAD + was included in the perfusate. Also, using heterologous expression systems, we confirmed the NAD + activation occurs directly on Slack channels and have identified the NAD + binding site using site-directed mutagenesis. The modulation of K Na channels by NAD + decreases the Na + concentration required for activation and now brings the EC 50 for K Na channels to a more physiologically relevant level. These results strongly suggest that that K Na channels can control neuronal excitability, such as regulating the resting membrane potential and shaping single and multiple action potentials.